The most representative symptom reported by patients suffering diseases such as arthritis is pain in the affected area. This pain can aggravate the condition through a neurogenic inflammation. Namely, an arthritic pain due to inflammation in a peripheral tissue stimulates a primary afferent nerve fiber through various mediators that carries the inflammation, and thus excitability of the primary afferent nerve fiber is increased. The increase in excitability reaches spinal neurons, and as a result, hyperalgesia is induced. Therefore, a full knowledge of the pain will play an important role in understanding and overcoming the disease.
There are various behavioral testing methods, using lab animals, for inspecting the degree of pain due to a disease such as arthritis. A method of measuring the degree of pain is disclosed in articles: 1) Larsen et al., “Reduction in Locomotor Activity of Arthritic Rats as Parameter for Chronic Pain: Effect of Morphine, Acetylsalicylic Acid and Citalopram,” Acta Pharmacol. Et Toxicol., 57:345-351 (1985); 2) Cain et al., “Pain-Related Disability and Effects of Chronic Pain,” Physiology & Behavior, 62(1):199-205 (1997); 3) Hallas et al., “Establishment of Behavioral Parameters For The Evaluation of Osteopathic Treatment Principles in a Rat Model of Arthritis,” JAOA, 97(4):207-214 (1997), and so on. In this method, a decrease of whole activities of a lab animal having arthritis in a leg is expressed numerically by recording changes in the activities of the lab animal through video analysis. The decrease of whole activity of the lab animal is due to an arthritic pain. This method is considered as a highly reliable test because it can quantify the decrease of the whole activities of lab animals. However, defining whether or not whole activities directly relate to the pain is difficult. Also, the method is very expensive and takes much time.
Another method of measuring the arthritic pain felt by a lab animal is disclosed in articles: 1) Sluka et al., “Different Effects of N-methyl-D-Aspartate (NMDA) and non-NMDA Receptor Antagonists on Spinal Release of Amino Acids After Development of Acute Arthritis In Rats,” Brain Research, 664:77-84 (1994); 2) Lawand et al., “Nicotinic Cholinergic Receptors: Potential Targets for Inflammatory Pain Relief,” Pain, 80:291-299 (1999); and 3) Lu et al., “Gabapentin Attenuates Nociceptive Behaviors in an Acute Arthritis Model in Rats,” The Journal of Pharmacology and Experimental Therapeutics, 290(1):214-219 (1999). In this method, arthritis is induced in the right leg of a lab animal such as a rat by injecting kaolin and carrageenan (suspended in normal saline) into the knee joint cavity and then the sole of the right foot is stimulated with heat. Thereafter, latency of leg withdrawal response to the heat is measured as a degree of the pain. However, the response of the leg with respect to the heat is considered as a secondary hyperalgesia that inflammation of the knee affects the leg by sensitization of central neuron. Therefore, ascertaining whether or not the method measures the pain caused by the inflammation induced in the knee is difficult.
Further, alternative methods of evaluating inflammation caused in a leg by threshold for vocalization or local temperature are known. The threshold value is measured when an inflamed leg of a lab animal is stimulated with pressure and thus the lab animal shrieks with pain, and the local temperature is measured at an inflamed portion. However, the threshold value and the local temperature are not objective and quantitative factors for representing change in primary behavior aspect induced by the pain.
In order to conduct a more accurate behavioral test, a method of evaluating an arthritic pain using decrease of a weight load applied in an inflamed leg of a lab animal is disclosed in articles: 1) Okuda et al., “Arthritis Induced in Cat by Sodium Urate: A Possible Animal Model for Tonic Pain,” Pain, 18:287-297 (1984); 2) Clarke, K. A., “Differential Fore-and Hindpow Force Transmission in the Walking Rat,” Physiology & Behavior, 58(3):415-419 (1995); 3) Clarke et al., “Gait Analysis in a Rat model of Osteoarthrosis,” Physiology & Behavior, 62(5):951-954 (1997); and 4) Schott et al., “Weight Bearing as an Objective Measure of Arthritic Pain in the Rat,” Journal of Pharmacological and Toxicological Methods, 31(2):79-83 (1994). Such a method is based on the fact that the weight load applied in the inflamed leg is decreased due to the arthritic pain. The decrease of the weight load is considered as an objective and quantitative index for representing change of primary behavior aspect induced by the pain. However, typically, the weight load of the inflamed leg of the lab animal is measured under the condition that the lab animal is made to stand up or remain a stationary state. In this case, the lab animal is stressed because it cannot move. As a result, the decrease of the weight load is changed depending on a pose or a stress of the lab animal. In addition, the decrease of the weight load appears more precisely when the lab animal is moving freely. Therefore, it is necessary to minimize artificial restraining or manipulations of experimental animals during measuring of the weight load.
In clinical situation, arthritic pain has been measured indirectly by patient's subjective appeal. If there is a method or device that could objectively measure arthritic pain, the degree of objective pain will be accepted as an index of effect of therapeutic intervention. Therefore, it is necessary to measure objectively the degree of arthritic pain in the clinical situation.